Isolation of Antiosteoporotic Compounds from Seeds of Sophora japonica

Abstract

Chemical investigation of Sophora japonica seeds resulted in the isolation of seven metabolites identified as: genistin (1), sophoricoside (2), sophorabioside (3), sophoraflavonoloside (4), genistein 7,4’-di-O-β-D-glucopyransoide (5), kaempferol 3-O-α–L-rhamnopyranosyl(1→6)β-D-glucopyranosyl(1→2)β-D-glucopyranoside (6) and rutin (7). Compounds 1, 2 and 5 showed significant estrogenic proliferative effect in MCF-7 cell in sub-cytotoxic concentration range. Compounds 1 and 2 showed minimal cell membrane damaging effect using LDH leakage assay. Accordingly, compound 2 (sophoricoside, (SPH)) was selected for further in-vivo studies as a potential anti-osteoporosis agent. The anti-osteoporotic effect of SPH was assessed in ovarectomized (OVX) rats after oral administration (15 mg/kg and 30 mg/kg) for 45 days compared to estradiol (10 µg/kg) as a positive control. Only in a dose of 30 mg/kg, SPH regained the original mechanical bone hardness compared to normal non-osteoporotic group. However, SPH (15 mg/kg) significantly increased the level of alkaline phosphatase (ALP) to normal level. Treatment with SPH (30 mg/kg) increased the level of ALP to be higher than normal group. SPH (15 mg/kg) did not significantly increase the serum level of osteocalcin (OC) compared to OVX group. On the other hand, treatment with SPH (30 mg/kg) significantly increased the level of OC to 78% higher than normal non-ovarectomized animals group. In addition, SPH (15 mg/kg) decreased the bone resorption marker, acid phosphatase (ACP) to normal level and SPH (30 mg/kg) further diminished the level of serum ACP. Histopathologically, sophoricoside ameliorated the ovarectomy induced osteoporosis in a dose dependent manner. The drug showed thicker bony trabeculae, more osteoid, and more osteoblastic rimming compared to OVX group.

Cysteine Prevents Menopausal Syndromes in Ovariectomized Mouse

“…27,47 The serum ALP level and trabecular bone parameters were reduced in the OVX mice. 48,49 A phytoestrogen treatment increased the serum ALP level, femur BMD, and trabecular bone formation in the OVX mice. 48,50 In the tibia metaphysis, the Cys treatment induced better responses in the BMD, BV/TV, TbN, ConnD, and porosity values which were comparable to those in the OVX mice.…”

Glutamic acid ameliorates estrogen deficiency–induced menopausal-like symptoms in ovariectomized mice

“…The serum ALP level and trabecular bone parameters were decreased in the OVX mice [59]. However, E 2 administration improved the serum ALP level and trabecular bone parameters in the OVX mice [59,60]. Glutamic acid also increased the serum ALP level in the OVX mice.…”

左卡尼汀(而非辅酶q10)提高阿托伐他汀在切除卵巢的老鼠的抗骨质疏松作用

“…The load values needed to break the femur in the horizontal and vertical directions significantly decreased in OVX rats to 34% and 56% of that needed for a normal femur, respectively. Estrogen (10 mg/kg) did not affect bone strength in the horizontal direction but significantly improved it in the vertical direction by 89.3% (Abdallah et al, 2014). In OVX rats, atorvastatin prevented the OVX-induced decreases in BMD and bone strength, improved bone hardness by about 43.3% restoring the original horizontal bone hardness, and repaired structure of both cortical and trabecular bone matrices in the head of the femur (Uyar et al, 2009).…”

“…The ovariectomy-induced increase in bone turnover is manifest by significant increases of serum levels of ALP (a marker of bone formation) (Seif, 2014) and acid phosphatase (ACP, a marker of bone resorption). Estrogen therapy significantly decreased ACP level to near 17.2% of its level in the OVX group (Abdallah et al, 2014). There is a link between strength of femur neck and BMC in rats and thus fracture risk in osteoporosis is closely related to quality of the cortical bone (Nakamura et al, 2008).…”

“…Femur breaking strength was measured by a three-point bending test using the hardness tester (Erweka GmbH, Heusenstamm, Germany) as previously described by Ko et al (2012) with minor modification by Abdallah et al (2014). The length of left femur was measured, its center was marked, and then it was placed in the clamp assembly of the tester in a position horizontal to the force direction.…”